Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Neurology. 2012 Aug 14;79(7):659-67. doi: 10.1212/WNL.0b013e318264e353. Epub 2012 Jul 11.
Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.
Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.
In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.
Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.
在最近一项基于白种人人群的帕金森病（PD）全基因组关联研究的荟萃分析中，有 11 个遗传位点达到了全基因组显著水平。这些遗传效应在不同人群中的一致性程度尚不清楚。
邀请帕金森病遗传流行病学联盟的研究人员参与这项研究。在 8750 例病例和 8955 例对照中，共对 11 个 SNP 进行了基因分型。采用固定效应模型和随机效应模型提供这些变体的汇总风险估计值。我们评估了研究之间的异质性以及不同祖源人群之间的异质性。
在总体分析中，9 个基因座的单核苷酸多态性（SNP）与保护性等位基因比值的显著关联，每等位基因比值为 0.78-0.87（LAMP3、BST1 和 MAPT），以及易感性每等位基因比值为 1.14-1.43（STK39、GAK、SNCA、LRRK2、SYT11 和 HIP1R）。在 9 个复制的 SNP 中，有 5 个 SNP 的效应大小存在名义上的显著站点间异质性（I²估计值范围为 39%-48%）。按种族亚组分析显示，BST1（rs11724635）在亚洲人群与白种人群中的效应显著更强，而 SNCA、LRRK2、LAMP3、HIP1R 和 STK39 在亚洲和白种人群中的效应相似，而 MAPT rs2942168 和 SYT11 rs34372695 在亚洲人群中是单态性的，突出了 PD 中人群特异性异质性的作用。
我们的研究使我们能够深入了解新发现的导致 PD 的遗传因素的分布，并表明在不同人群中进行大规模评估对于理解人群特异性异质性的作用非常重要。
